Ophthalmologists who occasionally encounter cases of noninfectious uveitis can—and should—glean several important therapeutic messages from the results of the Multicenter Uveitis Steroid Treatment (MUST) Trial, according to the study’s chairman, Douglas A. Jabs, MD, MBA. Eye M.D.s are likely to be surprised by some of the study’s conclusions about systemic corticosteroid therapy, he said. Dr. Jabs is professor and chairman of ophthalmology at the Mount Sinai School of Medicine, New York, N.Y.

“The piece of it that really surprises most clinicians is how little problem we encountered with corticosteroids. But that’s because they don’t know that the goal is to use immunosuppressants to reduce the corticosteroid dosage to below 10 mg per day,” Dr. Jabs said. “We found that the risk of side effects from systemic corticosteroid therapy is very small, if it is done properly.”

MUST investigators randomized 255 patients with noninfectious intermediate uveitis, posterior uveitis or panuveitis (479 eyes) either to systemic corticosteroids plus immunosuppression or to localized therapy with a fluocinolone acetonide implant. The results after two years of follow-up were published in Ophthalmology.1

Dr. Jabs identified six take-home messages from MUST for ophthalmologists who do not specialize in uveitis:

Equal effectiveness. Both the systemic approach and implant therapy controlled inflammation in a majority of cases, and they were equivalent at improving vision over 24 months of follow-up. “In terms of patient management, you can use either one and have a good outcome,” he said.

Implant therapy works. Not only does the implant work as well as systemic therapy but it also offers an alternative based on the individual’s disease course or other needs. In the trial, patients gave slightly higher quality-of-life scores to the implant than to systemic therapy.

The implant has an edge with inflammation. The implant controlled inflammation faster, and slightly better, than systemic therapy. “The data suggest that the implant might be better for patients who are failing systemic therapy. There’s a role for the implant in that situation.”

More ocular side effects with the implant. Nearly all of the phakic eyes with implants developed cataracts requiring surgery, and 25 percent of the eyes required surgery to reduce IOP. “It’s not that systemic therapy doesn’t have ocular side effects; it’s just that the implant has more of them,” Dr. Jabs said.

Add immunosuppression. Corticosteroid-related side effects—including weight gain—are minimal at systemic dosages below 10 mg daily, but such a low dosage is possible only when paired with immunosuppression. “Many ophthalmologists overuse corticosteroids and underuse immunosuppressants,” he said. “If you’re not comfortable using immunosuppressants, refer the patient to someone who is.”

Close monitoring is essential. Whether they are on systemic or implant therapy, these patients must be examined frequently to assure the inflammation remains under control and to catch side effects early, Dr. Jabs said. He sees his uveitis patients monthly.

The MUST trial results confirmed the recommendations that an expert panel made a decade ago about the use of corticosteroid-sparing immunosuppressive therapy to control the chronic inflammation of uveitis.2 But many patients continue to be maintained indefinitely on large doses of corticosteroids, a 2011 study found.3

Immunosuppression remains underused because of fear, Dr. Jabs said. “The potential side effects from immunosuppression are life threatening. The average ophthalmologist in the community, who doesn’t see patients with severe uveitis all the time, doesn’t feel comfortable managing the potential side effects from immunosuppressants,” he said. In such cases, the patient should be referred immediately to somebody who knows how to use these drugs, he said. “As the MUST trial showed, then you have an excellent chance of controlling the inflammation and improving visual function with minimal systemic side effects,” Dr. Jabs said.

If you have a Fuchs patient with corneal thickening up to 620 ?m who needs cataract surgery, are you safe simply doing phaco, or should you add a DSAEK procedure? That was the basic question posed to comprehensive ophthalmologists in a recent survey.

The great majority—approximately 90 percent—would perform phaco alone, either as a routine procedure or with special steps such as adding BSS Plus or Viscoat. The remainder would also perform DSAEK or refer to a cornea specialist.

How do specialists make this calculation? Douglas D. Koch, MD, professor of ophthalmology at Baylor College of Medicine in Houston, said he, too, often can avoid DSAEK with central corneal pachymetry measurements up to 620 to 630 ?m. There is also the rare patient with pachymetry in this range with a normal endothelium for whom these concerns are not relevant.

“You have to weigh other factors in this decision,” said Dr. Koch. “Sometimes DSAEK doesn’t result in 20/20 vision because of the lamellar interface. On the other hand, some patients with Fuchs dystrophy have an irregular posterior surface that, independent of any corneal edema, results in visual loss to 20/30 or worse; these patients might benefit from having a DSAEK at the same time.”

One factor that surgeons must consider is selection of IOL power, said Dr. Koch. “DSAEK typically creates a hyperopic shift of a diopter or slightly more.” So if you have a patient who might need a DSAEK in the near future, you might be better off aiming for a little bit of myopia.

This is a case that requires sound clinical judgment, said Dr. Koch. It involves assessing factors such as clinical history, comparisons with the other eye, endothelial cell count, the presence and severity of visual symptoms attributable to corneal disease, and age of the patient. “You also feel better about targeting toward emmetropia if it’s a relatively soft cataract and widely dilating pupil [so DSAEK is unlikely to be needed],” said Dr. Koch. However, surgery for an extremely brunescent lens with floppy iris syndrome is more likely to result in damage to the corneal endothelium and worsen the Fuchs, he said.

As for the need to take special precautions during phaco with these patients, Dr. Koch stresses that the critical piece is assiduously protecting the corneal endothelium during the phaco procedure. “I typically use both dispersive and viscoadaptive ophthalmic viscosurgical devices in order to shield the endothelium from any direct surgical trauma.”

—Annie Stuart

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Dr. Koch is a consultant for Alcon and AMO.
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FOR MORE ON THIS TOPIC, see “Patients With Fuchs and Cataract: Staged or Combined Procedures?” page 25.

CLINICAL PREFERENCES. To better understand current practices on a number of topics, the Academy surveyed comprehensive ophthalmologists about how they would handle various clinical situations. Each month, EyeNet will feature one question—this month about management of Fuchs patients with cataract—and ask an expert to provide perspective on the responses.

A study to evaluate more definitively the long-suspected link between aspirin use and age-related macular degeneration (AMD) shows an association between frequent consumption of the anti-inflammatory agent and likelihood of disease severity. 1 However, this is not evidence for making any recommendations, said Usha Chakravarthy, MD, PhD, coauthor of the study and professor of ophthalmology at Queen’s University in Belfast, United Kingdom.

The European Eye (EUREYE) Study involved nearly 4,700 participants aged 65 years or older from seven sites in Europe. It was divided into four groups, ranging from those who never took aspirin to daily users. About one-third of participants who developed wet AMD were daily consumers, whereas 16 percent of those without AMD took aspirin every day—a significant difference, even when adjusted for age, gender and other health factors. However, Dr. Chakravarthy cautioned, “All the EUREYE study did is to report the associations.”

Fewer markers of vascular risk were reported in the daily-aspirin group, but there was an increased risk of early AMD and late wet AMD. Does this suggest that daily aspirin improves cardiovascular health—but heightens AMD risk? “This was a cross-sectional study, and hence, it is not possible to make such assumptions,” Dr. Chakravarthy said.

What the results do underscore is that “each patient should be considered individually,” said Anne E. Fung, MD, a retina specialist with Pacific Eye Associates in San Francisco. Is there a high risk of cardiovascular disease? Then frequent aspirin may be beneficial. Conversely, if an older patient has risk factors for AMD, then warning against frequent aspirin use might be warranted, she said.

A comprehensive review of a patient’s medical history is necessary before any recommendations are made—and this applies to providing advice about supplements, not just aspirin, Dr. Fung said.

The study is “hardly damning” of aspirin, agreed geriatric researcher Richard Schamp, MD, associate professor of community and family medicine at Saint Louis University. To establish causation, a large, interventional investigation is needed, he said.

In the first clinical trial of idebenone for Leber hereditary optic neuropathy, some patients who received the drug experienced improvements in visual acuity and color perception.1

Researchers in the Rescue of Hereditary Optic Disease Outpatients Study (RHODOS) enrolled 85 patients with LHON in Germany, Canada and the United Kingdom and randomly assigned 55 to receive 900 mg of idebenone daily; the remaining 30 received placebo during the 24-week trial.

The study’s primary end point (best recovery in visual acuity) did not achieve statistical significance. But, in those patients with unequal visual acuities in the two eyes at baseline, all secondary end points regarding improvements in visual acuity were statistically significant (i.e., changes in visual acuity of the best eye at baseline, changes in visual acuity for both eyes in each patient). Moreover, in the subgroup of patients whose visual acuity was “off chart” at baseline, 12 of 61 eyes treated with idebenone experienced VA improvement that allowed reading of at least one full line on the chart at week 24, compared with none of 29 eyes in the placebo group.

Notably, the researchers said, idebenone appeared to prevent further visual loss among patients with unequal visual acuities. They said that these individuals may be in earlier stages of the disease and have the greatest potential visual reserve. Therefore, they may obtain the greatest clinical benefit in terms of preventing additional visual loss.

“It is very difficult to find significant results in a cohort of 85 patients. That is the implicit problem in rare diseases: It is mostly not possible to design trials large enough to find mild drug effects,” said lead researcher Thomas Klopstock, MD, professor of neurology at the University of Munich and coordinator of mitoNET, the German network for mitochondrial disorders. “That is, however, why we believe in idebenone in LHON. Although the primary end point missed significance, all analyses taken together point consistently in the direction of efficacy.”

Dr. Klopstock noted, however, that it will be difficult to conduct a second trial to confirm the results, “given the rarity of the disease and the fact that LHON patients all over the world already ask for idebenone and may take it as an over-the-counter drug.” (Editor’s note: Idebenone, a quinone analogue of coenzyme Q10, is not FDA approved.)